title: Identification and evolution of venom phospholipase A2 inhibitors from Protobothrops elegans serum.
abstract: The cDNAs encoding venom phospholipase A(2) (PLA(2)) inhibitors (PLIs), named Protobothrops elegans (Pe)γPLI-A, PeγPLI-B, PeαPLI-A, and PeαPLI-B, were cloned from the P. elegans liver cDNA library. They were further divided into several constituents due to nucleotide substitutions in their open reading frames. For PeαPLI-A, two constituents, PeαPLI-A(a) and PeαPLI-A(b), were identified due to three nonsynonymous substitutions in exon 3. Far-western blot and mass-spectrometry analysis of the P. elegans serum proteins showed the presence of γPLIs, and αPLIs, which can bind venom PLA(2)s. In αPLIs from Protobothrops sera, A or B subtype-specific amino acid substitutions are concentrated only in exon 3. A comparison of γPLIs showed that γPLI-As are conserved and γPLI-Bs diversified. Mathematical analysis of the nucleotide sequences of Protobothrops γPLI-B cDNAs revealed that the particular loops in the three-finger motifs diversified by accelerated evolution. Such evolutionary features should have made serum PLIs acquire their respective inhibitory activities to adapt to venom PLA(2) isozymes.
authors.affiliation: Department of Applied Life Science, Faculty of Bioscience and Biotechnology, Sojo University, Ikeda, Kumamoto, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: So
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Murakami
authors.forename: Naoki
authors.initials: N
authors.lastname: Ikeda
authors.forename: Takahito
authors.initials: T
authors.lastname: Chijiwa
authors.forename: Naoko
authors.initials: N
authors.lastname: Oda-Ueda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuraishi
authors.forename: Shosaku
authors.initials: S
authors.lastname: Hattori
authors.forename: Motonori
authors.initials: M
authors.lastname: Ohno
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D026481:Blotting, Far-Western; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000097:blood / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis*; D004926:Escherichia coli; D019143:Evolution, Molecular; D005091:Exons; D015723:Gene Library; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000097:blood; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D044967:Serum / Q000737:chemistry; D017841:Trimeresurus / Q000097:blood / Q000235:genetics
chemical_list: D001798:Blood Proteins; D003435:Crotalid Venoms; D018076:DNA, Complementary; C400481:PLIalpha; D064801:Phospholipase A2 Inhibitors; D020033:Protein Isoforms; D011994:Recombinant Proteins; D054467:Phospholipases A2